Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT

Jim Hyun Kim, Sun Mi Park, Mi Ran Kang, Sue Young Oh, Tae H. Lee, Mark T. Muller, In Kwon Chung

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Telomere homeostasis is regulated by telomerase and a collection of associated proteins. Telomerase is, in turn, regulated by post-translational modifications of the rate-limiting catalytic subunit hTERT. Here we show that disruption of Hsp90 by geldanamycin promotes efficient ubiquitination and proteasome-mediated degradation of hTERT. Furthermore, we have used the yeast two-hybrid method to identify a novel RING finger gene (MKRN1) encoding an E3 ligase that mediates ubiquitination of hTERT. Overexpression of MKRN1 in telomerase-positive cells promotes the degradation of hTERT and decreases telomerase activity and subsequently telomere length. Our data suggest that MKRN1 plays an important role in modulating telomere length homeostasis through a dynamic balance involving hTERT protein stability.

Original languageEnglish
Pages (from-to)776-781
Number of pages6
JournalGenes and Development
Volume19
Issue number7
DOIs
Publication statusPublished - 2005 Apr 1

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT'. Together they form a unique fingerprint.

  • Cite this